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1.
J Econ Entomol ; 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39350334

ABSTRACT

Thaumatotibia leucotreta Meyrick (Lepidoptera: Tortricidae) is a major threat to the production and marketing of pepper (Capsicum spp.) in Ghana. To reduce the damage of the pest on pepper farming, it is important to find appropriate control methods, which may include the use of resistant host plants. This study investigated the relative susceptibility of 6 pepper varieties commonly cultivated in Ghana: Legon 18, Bird's eye, Scotch bonnet, Cayenne, KA2, and sweet pepper (Yolo wonder+ variety). Choice and no-choice ovipositional preference tests were conducted and the population growth rate of T. leucotreta was determined by establishing life table parameters including the net reproductive rates (R0), the mean generation time (G), intrinsic rate of natural increase (rm), the population doubling time (T), and the finite rate of increase (λ). In the no-choice test, females exhibited oviposition preference for sweet pepper (12.08 eggs/fruit), while Bird's eye was the least preferred (5.00 eggs/fruit). The same results were observed in the choice test. However, the population growth rate of T. leucotreta was highest on the Scotch bonnet and Cayenne, with rm of 0.124 and 0.127, respectively, while the Bird's eye and sweet pepper recorded the least rm of 0.116. Thus, the tested varieties had varying levels of susceptibility to T. leucotreta infestation. Bird's eye was the least susceptible variety, while Cayenne and Scotch bonnet were the most susceptible varieties. These findings could direct farmers on the choices of pepper varieties for cultivation and proffer potential opportunities to breed new varieties resistant to T. leucotreta infestation.

3.
J Psychiatr Pract ; 30(5): 349-356, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39357016

ABSTRACT

This column is the third in a 3-part series describing cases in which general medical knowledge, including psychiatric and clinical pharmacology, was instrumental in determining whether dereliction was the direct cause of damages in a malpractice suit. This case illustrates how not taking into account the following variables can result in a false-positive diagnosis of a lethal serotonin syndrome: (a) the time course of treatment, (b) the time course of symptoms, (c) the difference between antemortem plasma and postmortem whole-blood levels of highly protein bound and highly lipophilic drugs. The case also illustrates how taking those 3 variables into account led to the conclusion that there was no dereliction in the care of the patient that was the direct cause of his death, and hence, there was no medical malpractice.


Subject(s)
Selective Serotonin Reuptake Inhibitors , Serotonin Syndrome , Sertraline , Humans , Serotonin Syndrome/diagnosis , Serotonin Syndrome/blood , Serotonin Syndrome/chemically induced , Male , Selective Serotonin Reuptake Inhibitors/pharmacology , False Positive Reactions , Adult , Middle Aged
4.
Clin Epidemiol ; 16: 683-697, 2024.
Article in English | MEDLINE | ID: mdl-39386131

ABSTRACT

Background: A substantial proportion of adults receive statins for treatment of hypercholesterolemia and cardiovascular risk, and statins have been found to improve outcomes in this patient population. However, studies have not consistently demonstrated the potential benefits of statins in preventing venous thromboembolism (VTE). Therefore, we conducted this study to investigate this association. Methods: We conducted a cohort analysis in a study sample comprised of 40-79-year-old patients with hyperlipidemia who received at least one fibrate or statin prescription between January 1995 and December 2018 in the United Kingdom Clinical Practice Research Datalink (CPRD) GOLD. We evaluated the association between statin use and incident unprovoked VTE, compared to fibrate use, an active comparator, using Kaplan-Meier (KM) analysis, Poisson regression (with and without propensity score matching), and inverse probability of treatment weights (IPTW) marginal structural models (MSM). Results: In this cohort of 166,292 patients with hyperlipidemia, 0.81% (N=1,353) developed incident unprovoked VTE. In analyses using the KM method, patients who received statins had a slightly lower risk of VTE compared to those who received fibrates (Log rank test: p=0.0524). The adjusted incident rate ratio (95% CI) for VTE, calculated using Poisson regression, controlling for serum cholesterol and other baseline covariates, in patients prescribed statins compared to fibrates was 0.77 (0.45-1.33) in the full cohort, 0.74 (0.38-1.45) in the propensity score matched analysis, and 0.51 (95% conservative CI: 0.34-0.76) in the IPTW MSM analysis. Conclusion: While the magnitude of effect varied across the different analytic methods, there is consistent evidence for a protective effect of statin use on the occurrence of unprovoked VTE.

5.
J Am Coll Cardiol ; 84(15): 1436-1454, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39357941

ABSTRACT

This consensus statement emerges from collaborative efforts among leading figures in critical care cardiology throughout the United States, who met to share their collective expertise on issues faced by those active in or pursuing contemporary critical care cardiology education. The panel applied fundamentals of adult education and curriculum design, reviewed requisite training necessary to provide high-quality care to critically ill patients with cardiac pathology, and devoted attention to a purposeful approach emphasizing diversity, equity, and inclusion in developing this nascent field. The resulting paper offers a comprehensive guide for current trainees, with insights about the present landscape of critical care cardiology while highlighting issues that need to be addressed for continued advancement. By delineating future directions with careful consideration and intentionality, this Expert Panel aims to facilitate the continued growth and maturation of critical care cardiology education and practice.


Subject(s)
Cardiology , Critical Care , Cardiology/education , Humans , Critical Care/standards , United States , Curriculum , Minnesota , Education, Medical, Graduate/methods
6.
J Chem Theory Comput ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39360658

ABSTRACT

We present the implementation of the Hubbard (U) and Hund (J) corrected Density Functional Theory (DFT + U + J) functionality in the Quickstep program, which is part of the CP2K suite. The tensorial and Löwdin subspace representations are implemented and compared. Full analytical DFT + U + J forces are implemented and benchmarked for the tensorial and Löwdin representations. We also present the implementation of the recently proposed minimum-tracking linear-response method that enables the U and J parameters to be calculated on first-principles basis without reference to the Kohn-Sham eigensystem. These implementations are benchmarked against recent results for different materials properties including DFT + U band gap opening in NiO, the relative stability of various polaron distributions in TiO2, the dependence of the calculated TiO2 band gap on +J corrections, and, finally, the role of the +U and +J corrections for the computed properties of a series of the hexahydrated transition metals. Our implementation provides results consistent with those already reported in the literature from comparable methods. We conclude the contribution with tests on the influence of the Löwdin orthonormalization on the occupancies, calculated parameters, and derived properties.

7.
Onderstepoort J Vet Res ; 91(2): e1-e6, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39354784

ABSTRACT

The COVID-19 pandemic has caused the death of 7.1 million people worldwide as of 7 July 2024. In Nigeria, the first confirmed case was reported on 27 February 2020, subsequently followed by a nationwide spread of SARS-CoV-2 with morbidity and mortality reaching 267 173 and 3155, respectively, as of 7 July 2024. At the beginning of the pandemic, only a few public health laboratories in Nigeria had the capacity for SARS-CoV-2 molecular diagnosis. The National Veterinary Research Institute (NVRI), already experienced in influenza diagnosis, responded to the public health challenge for the diagnosis of COVID-19 samples from humans. The feat was possible through the collective utilisation of NVRI human and material resources, including biosafety facilities, equipment, reagents and consumables donated by international partners and collaborators. Within 6 months of the reported COVID-19 outbreak in Nigeria, over 33 000 samples were processed in NVRI facilities covering five states. Thereafter, many field and laboratory projects were jointly implemented between NVRI and collaborating sectors including the Nigerian Centre for Disease Control (NCDC) and the National Institute for Medical Research (NIMR), which brought together professionals in the health, veterinary, education and socio-sciences. In addition, One Health grants were secured to enhance surveillance for coronavirus and other zoonoses and build capacity in genomics. Bio-surveillance for coronaviruses and other emerging zoonotic pathogens at the human-animal interface was activated and continued with sample collection and analysis in the laboratory for coronaviruses, Lassa fever virus and Mpox. One Health approach has shown that inter-sectoral and multinational collaboration for diagnosis, research and development in animals, and the environment to better understand pathogen spillover events at the human-animal interface is an important global health priority and pandemic preparedness.


Subject(s)
COVID-19 , One Health , Animals , Humans , COVID-19/epidemiology , COVID-19/veterinary , COVID-19/prevention & control , Nigeria/epidemiology , Pandemics , Public Health
8.
World J Microbiol Biotechnol ; 40(11): 333, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39358646

ABSTRACT

The Staphylococcus genus comprises multiple pathogenic and opportunistic species that represent a risk to public health. Epidemiological studies require accurate taxonomic classification of isolates with enough resolution to distinguish clonal complexes. Unfortunately, 16 S rRNA molecular analysis and phenotypic characterization cannot distinguish all species and do not offer enough resolution to assess intraspecific diversity. Other approaches, such as Multilocus Sequence Tagging, provide higher resolution; however, they have been developed for Staphylococcus aureus and a few other species. Here, we developed a set of genus-targeted primers using five orthologous genes (pta, tuf, tpi, groEs, and sarA) to identify all Staphylococcus species within the genus. The primers were initially evaluated using 20 strains from the Collection of Microorganisms of Interest in Animal Health from AGROSAVIA (CMISA), and their amplified sequences were compared to a set of 33 Staphylococcus species. This allowed the taxonomic identification of the strains even on close species and the establishment of intraspecies diversity. To enhance the scope and cost-effectiveness of the proposed strategy, we customized the primer sets for an Illumina paired-end amplicon protocol, enabling gene multiplexing. We assessed five genes across 177 strains, generating 880 paired-end libraries from the CMISA. This approach significantly reduced sequencing costs, as all libraries can be efficiently sequenced in a single MiSeq run at a fraction (one-fourth or less) of the cost associated with Sanger sequencing. In summary, this method can be used for precise identification and diversity analysis of Staphylococcus species, offering an advancement over traditional techniques in both resolution and cost-effectiveness.


Subject(s)
Coagulase , DNA, Bacterial , RNA, Ribosomal, 16S , Staphylococcus , Staphylococcus/genetics , Staphylococcus/classification , Staphylococcus/isolation & purification , Staphylococcus/enzymology , Coagulase/metabolism , Coagulase/genetics , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , DNA Primers/genetics , Phylogeny , Staphylococcal Infections/microbiology , Animals , Genes, Bacterial/genetics , Bacterial Proteins/genetics , Sequence Analysis, DNA , Multilocus Sequence Typing , Bacterial Typing Techniques/methods , Genetic Markers , High-Throughput Nucleotide Sequencing
9.
Prehosp Emerg Care ; : 1-9, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39374029

ABSTRACT

OBJECTIVES: Current guidelines for parameters of the delivery of chest compressions (CC) for infants and children are largely consensus based. Of the two recommended depth targets - 1.5 inches and 1/3 anterior-posterior chest diameter (APD) - it is unclear whether these have equal potential for injury. In previous experiments, our group showed in an animal model of pediatric asphyxial out-of-hospital cardiac arrest (OHCA; modeling ∼ 7 year-old children) that 1/3 APD resulted in significantly deeper CC and a higher likelihood of life-threatening injury. We sought to examine and compare injury characteristics of CC delivered at 1.5 inches or 1/3 APD in an infant model of asphyxial OHCA. METHODS: Swine were sedated, anesthetized, paralyzed, intubated through direct laryngoscopy, and then mechanically ventilated (10ml/kg, FiO2:21%). APD was measured and confirmed by two investigators via a sliding T-square at the xiphoid. After instrumentation for vital signs monitoring, and while still anesthetized, the endotracheal tube was manually occluded to induce asphyxia, and occlusion was maintained for 9 minutes. Animals were then randomized to receive CC with a depth of 1.5 inches (Group 1) or 1/3 APD (Group 2), both with a rate of 100 per minute. Advanced life support drugs were administered at 13 minutes, and defibrillation at 14 minutes. Resuscitation continued until return of spontaneous circulation (ROSC) or 20 minutes of failed resuscitation. Survivors were sacrificed with KCl after 20 minutes of observation. Veterinary staff conducted necropsy to assay lung injury, rib fracture, hemothorax, airway bleeding, great vessel dissection, and heart/liver/spleen contusion. Injury characteristics were summarized and compared via Chi-Squared test or Mann-Whitney U-test using an alpha = 0.05. RESULTS: A total of 36 animals were included for analysis (Group 1: 18; Group 2: 18). Mean (SD) APD overall was 5.58 (0.23) inches, yielding a mean 1/3 APD depth of 1.86 inches. APD did not differ between groups. ROSC rates did not differ between groups. No injury characteristics differed significantly between groups. CONCLUSIONS: In an swine model of infant asphyxial OHCA and resuscitation considering 1/3 APD or 1.5 inches, neither CC depth strategy was associated with increased injury.

10.
Health Qual Life Outcomes ; 22(1): 72, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39218902

ABSTRACT

BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic disease resulting in progressive muscle weakness, loss of ambulation, and cardiorespiratory complications. Direct estimation of health-related quality of life for patients with DMD is challenging, highlighting the need for proxy measures. This study aims to catalog and compare existing published health state utility estimates for DMD and related conditions. METHODS: Using two search strategies, relevant utilities were extracted from the Tufts Cost-Effectiveness Analysis Registry, including health states, utility estimates, and study and patient characteristics. Analysis One identified health states with comparable utility estimates to a set of published US patient population utility estimates for DMD. A minimal clinically important difference of ± 0.03 was applied to each DMD utility estimate to establish a range, and the registry was searched to identify other health states with associated utilities that fell within each range. Analysis Two used pre-defined search terms to identify health states clinically similar to DMD. Mapping was based on the degree of clinical similarity. RESULTS: Analysis One identified 4,308 unique utilities across 2,322 cost-effectiveness publications. The health states captured a wide range of acute and chronic conditions; 34% of utility records were extrapolated for US populations (n = 1,451); 1% were related to pediatric populations (n = 61). Analysis Two identified 153 utilities with health states clinically similar to DMD. The median utility estimates varied among identified health states. Health states similar to the early non-ambulatory DMD phase exhibited the greatest difference between the median estimate of the sample (0.39) and the existing estimate from published literature (0.21). CONCLUSIONS: When available estimates are limited, using novel search strategies to identify utilities of clinically similar conditions could be an approach for overcoming the information gap. However, it requires careful evaluation of the utility instruments, tariffs, and raters (proxy or self).


Subject(s)
Muscular Dystrophy, Duchenne , Quality of Life , Humans , Health Status , Male , Registries , Cost-Benefit Analysis , Child , Quality-Adjusted Life Years
11.
J Am Coll Cardiol ; 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39230544

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) often remains undiagnosed, and it independently raises the risk of ischemic stroke, which is largely reversible by oral anticoagulation. Although randomized trials using longer term screening approaches increase identification of AF, no studies have established that AF screening lowers stroke rates. OBJECTIVES: To address this knowledge gap, the GUARD-AF (Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals) trial screened participants in primary care practices using a 14-day continuous electrocardiographic monitor to determine whether screening for AF coupled with physician/patient decision-making to use oral anticoagulation reduces stroke and provides a net clinical benefit compared with usual care. METHODS: GUARD-AF was a prospective, parallel-group, randomized controlled trial designed to test whether screening for AF in people aged ≥70 years using a 14-day single-lead continuous electrocardiographic patch monitor could identify patients with undiagnosed AF and reduce stroke. Participants were randomized 1:1 to screening or usual care. The primary efficacy and safety outcomes were hospitalization due to all-cause stroke and bleeding, respectively. Analyses used the intention-to-treat population. RESULTS: Enrollment began on December 17, 2019, and involved 149 primary care sites across the United States. The COVID-19 pandemic led to premature termination of enrollment, with 11,905 participants in the intention-to-treat population. Median follow-up was 15.3 months (Q1-Q3: 13.8-17.6 months). Median age was 75 years (Q1-Q3: 72-79 years), and 56.6% were female. The risk of stroke in the screening group was 0.7% vs 0.6% in the usual care group (HR: 1.10; 95% CI: 0.69-1.75). The risk of bleeding was 1.0% in the screening group vs 1.1% in the usual care group (HR: 0.87; 95% CI: 0.60-1.26). Diagnosis of AF was 5% in the screening group and 3.3% in the usual care group, and initiation of oral anticoagulation after randomization was 4.2% and 2.8%, respectively. CONCLUSIONS: In this trial, there was no evidence that screening for AF using a 14-day continuous electrocardiographic monitor in people ≥70 years of age seen in primary care practice reduces stroke hospitalizations. Event rates were low, however, and the trial did not enroll the planned sample size.(Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals [GUARD-AF]; NCT04126486).

12.
Neurotherapeutics ; : e00446, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39277505

ABSTRACT

Glycogen storage diseases (GSDs) comprise a group of inherited metabolic disorders characterized by defects in glycogen metabolism, leading to abnormal glycogen accumulation in multiple tissues, most notably affecting the liver, skeletal muscle, and heart. Recent findings have uncovered the importance of glycogen metabolism in the brain, sustaining a myriad of physiological functions and linking its perturbation to central nervous system (CNS) pathology. This link resulted in classification of neurological-GSDs (n-GSDs), a group of diseases with shared deficits in neurological glycogen metabolism. The n-GSD patients exhibit a spectrum of clinical presentations with common etiology while requiring tailored therapeutic approaches from the traditional GSDs. Recent research has elucidated the genetic and biochemical mechanisms and pathophysiological basis underlying different n-GSDs. Further, the last decade has witnessed some promising developments in novel therapeutic approaches, including enzyme replacement therapy (ERT), substrate reduction therapy (SRT), small molecule drugs, and gene therapy targeting key aspects of glycogen metabolism in specific n-GSDs. This preclinical progress has generated noticeable success in potentially modifying disease course and improving clinical outcomes in patients. Herein, we provide an overview of current perspectives on n-GSDs, emphasizing recent advances in understanding their molecular basis, therapeutic developments, underscore key challenges and the need to deepen our understanding of n-GSDs pathogenesis to develop better therapeutic strategies that could offer improved treatment and sustainable benefits to the patients.

13.
ACS Nano ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39282795

ABSTRACT

Increasing accumulation of nanoplastics across ecosystems poses a significant threat to both terrestrial and aquatic life. Surface-enhanced Raman scattering (SERS) is an emerging technique used for nanoplastics detection. However, the identification and classification of nanoplastics using SERS faces challenges regarding sensitivity and accuracy as nanoplastics are sparsely dispersed in the environment. Metal-phenolic networks (MPNs) have the potential to rapidly concentrate and separate various types and sizes of nanoplastics. SERS combined with machine learning may improve prediction accuracy. Herein, we report the integration of MPNs-mediated separation with machine learning-aided SERS methods for the accurate classification and high-precision quantification of nanoplastics, which is tailored to include the complete region of characteristic peaks across diverse nanoplastics in contrast to the traditional manual analysis of SERS spectra on a singular characteristic peak. Our customized machine learning system (e.g., outlier detection, classification, quantification) allows for the identification of detectable nanoplastics (accuracy 81.84%), accurate classification (accuracy > 97%), and sensitive quantification of various types of nanoplastics (polystyrene (PS), poly(methyl methacrylate) (PMMA), polyethylene (PE), and poly(lactic acid) (PLA)) down to ultralow concentrations (0.1 ppm) as well as accurate classification (accuracy > 92%) of nanoplastic mixtures at a subppm level. The effectiveness of this approach is substantiated by its ability to discern between different nanoplastic mixtures and detect nanoplastic samples in natural water systems.

14.
Kidney360 ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39283693

ABSTRACT

BACKGROUND: Multiple studies have shown that females are living donors for kidney transplantation at higher rates than males. However, the underlying reasons for this observation are not well-understood. We examined the living donor evaluation process to determine the point at which sex imbalance arises. Based on a previous study, we hypothesized that both sexes are equally likely to become approved as living donors, but females are more likely to follow through with donation. METHODS: Single institution retrospective chart review of self-referrals for living donor evaluation between 1/2009 - 12/2022. Self-referrals identified using the Organ Transplant Tracking Record database and cross referenced with billing data. Exclusion at each stage of evaluation was recorded and compared between sexes using log binomial regression; unadjusted and adjusted (for donor age, race, ethnicity, relationship to recipient, and recipient sex) risk ratios (RRs) with 95% confidence interval (CI) were determined. RESULTS: 1,861 self-referrals were reviewed, including 1,214 (65.2%) females and 647 (34.8%) males, resulting in 146 approvals and 125 donations (76/125, 60.8% females, 49/125 39.2% males). Adjusted RRs indicated no significant differences between sexes in completing medical and/or psychosocial workup, having medical and/or psychosocial contraindications, being approved for donation, and proceeding with donation. The top medical contraindications for both sexes were obesity, hypertension, and nephrolithiasis. CONCLUSION: Female overrepresentation among living donors is likely due to the 1.9 times higher rate of self-referral for evaluation. After this point, both sexes were equally likely to complete workup, be approved, and follow through with donation. Increased efforts to engage males at the initial self-referral stage has the potential to expand access to living donor kidney transplantation.

15.
J Int AIDS Soc ; 27(9): e26361, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39301675

ABSTRACT

INTRODUCTION: Globally, there have been significant declines in HIV incidence over the past two decades, but this decline is slowing, and in some settings, declines have stalled or are growing-particularly where epidemics are concentrated in key populations (KPs). Understanding temporal changes in HIV incidence among KP is critical yet, due to logistical constraints, there are few sources of longitudinal incidence data, particularly among KP. METHODS: We present HIV incidence rates from June 2014 to December 2022 among cisgender men who have sex with men (MSM) and people who inject drugs (PWID) attending community-based integrated care centres (ICCs) in 15 Indian cities. ICCs, established between 2014 and 2017, provide HIV testing and other services to MSM (eight sites) or PWID (eight sites). Client HIV testing data were included in the analysis if they had ≥2 tests and were not positive on the first test. We calculated incidence rates per 100 person-years (PY), stratified by KP, city/site and year. Poisson regression explored associations of incidence with time, age, gender (PWID only) and ICC use. RESULTS: From June 2014 to December 2022, 13,501 clients (5722 MSM, 7779 PWID) had ≥2 HIV tests over a median of 1.8 years. There were a total of 1093 incident HIV acquisitions. Overall incidence rates for MSM and PWID were 1.9/100 PY (95% CI: 1.7-2.2) and 4.1 (3.9-4.4), respectively. Among MSM sites, incidence ranged from 0.4 to 3.5 and in PWID sites from 0.6 to 17.9. From adjusted models, incidence increased by 17% annually among MSM. Among PWID, incidence increased by 11% annually up until 2020 and then decreased by 29% after 2020; when excluding the outlier of New Delhi, incidence was stable among PWID. MSM and PWID 21-25 years old had the highest risk of HIV and among PWID, those more consistently engaged in medication for opioid use disorder were at the lowest risk. CONCLUSIONS: While there was substantial geographic variability, MSM and PWID engaged in a free community-based clinic experienced persistently high HIV incidence (>2/100 PY). KP in low- and middle-income countries should be a focus when considering novel strategies such as long-acting pre-exposure prophylaxis to curtail incidence.


Subject(s)
HIV Infections , Homosexuality, Male , Substance Abuse, Intravenous , Humans , Male , Incidence , India/epidemiology , HIV Infections/epidemiology , HIV Infections/prevention & control , Adult , Homosexuality, Male/statistics & numerical data , Longitudinal Studies , Substance Abuse, Intravenous/epidemiology , Substance Abuse, Intravenous/complications , Young Adult , Adolescent , Middle Aged
16.
Emerg Microbes Infect ; 13(1): 2402880, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39259045

ABSTRACT

The recently dominant SARS-CoV-2 Omicron JN.1 has evolved into multiple sublineages, with recurrent spike mutations R346T, F456L, and T572I, some of which exhibit growth advantages, such as KP.2 and KP.3. We investigated these mutations in JN.1, examining their individual and combined effects on immune evasion, ACE2 receptor affinity, and in vitro infectivity. F456L increased resistance to neutralization by human sera, including those after JN.1 breakthrough infections, and by RBD class-1 monoclonal antibodies, significantly altering JN.1 antigenicity. R346T enhanced ACE2-binding affinity and modestly boosted the infectivity of JN.1 pseudovirus, without a discernible effect on serum neutralization, while T572I slightly bolstered evasion of SD1-directed mAbs against JN.1's ancestor, BA.2, possibly by altering SD1 conformation. Importantly, expanding sublineages such as KP.2 containing R346T, F456L, and V1104L, showed similar neutralization resistance as JN.1 with R346T and F456L, suggesting V1104L does not appreciably affect antibody evasion. Furthermore, the hallmark mutation Q493E in KP.3 significantly reduced ACE2-binding affinity and viral infectivity, without noticeably impacting serum neutralization. Our findings illustrate how certain JN.1 mutations confer growth advantages in the population and could inform the design of the next COVID-19 vaccine booster.


Subject(s)
COVID-19 , Immune Evasion , Mutation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Humans , SARS-CoV-2/genetics , SARS-CoV-2/immunology , COVID-19/virology , COVID-19/immunology , Antibodies, Neutralizing/immunology , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Viral/immunology , Antibodies, Monoclonal/immunology
17.
JMIR Form Res ; 8: e56962, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221852

ABSTRACT

BACKGROUND: The number of individuals using digital health devices has grown in recent years. A higher rate of use in patients suggests that primary care providers (PCPs) may be able to leverage these tools to effectively guide and monitor physical activity (PA) for their patients. Despite evidence that remote patient monitoring (RPM) may enhance obesity interventions, few primary care practices have implemented programs that use commercial digital health tools to promote health or reduce complications of the disease. OBJECTIVE: This formative study aimed to assess the perceptions, needs, and challenges of implementation of an electronic health record (EHR)-integrated RPM program using wearable devices to promote patient PA at a large urban primary care practice to prepare for future intervention. METHODS: Our team identified existing workflows to upload wearable data to the EHR (Epic Systems), which included direct Fitbit (Google) integration that allowed for patient PA data to be uploaded to the EHR. We identified pictorial job aids describing the clinical workflow to PCPs. We then performed semistructured interviews with PCPs (n=10) and patients with obesity (n=8) at a large urban primary care clinic regarding their preferences and barriers to the program. We presented previously developed pictorial aids with instructions for (1) providers to complete an order set, set step-count goals, and receive feedback and (2) patients to set up their wearable devices and connect them to their patient portal account. We used rapid qualitative analysis during and after the interviews to code and develop key themes for both patients and providers that addressed our research objective. RESULTS: In total, 3 themes were identified from provider interviews: (1) providers' knowledge of PA prescription is focused on general guidelines with limited knowledge on how to tailor guidance to patients, (2) providers were open to receiving PA data but were worried about being overburdened by additional patient data, and (3) providers were concerned about patients being able to equitably access and participate in digital health interventions. In addition, 3 themes were also identified from patient interviews: (1) patients received limited or nonspecific guidance regarding PA from providers and other resources, (2) patients want to share exercise metrics with the health care team and receive tailored PA guidance at regular intervals, and (3) patients need written resources to support setting up an RPM program with access to live assistance on an as-needed basis. CONCLUSIONS: Implementation of an EHR-based RPM program and associated workflow is acceptable to PCPs and patients but will require attention to provider concerns of added burdensome patient data and patient concerns of receiving tailored PA guidance. Our ongoing work will pilot the RPM program and evaluate feasibility and acceptability within a primary care setting.


Subject(s)
Electronic Health Records , Exercise , Obesity , Qualitative Research , Wearable Electronic Devices , Humans , Exercise/psychology , Male , Female , Obesity/therapy , Adult , Middle Aged , Primary Health Care
18.
Article in English | MEDLINE | ID: mdl-39243255

ABSTRACT

BACKGROUND: Although targeting atrial fibrillation (AF) drivers and substrates has been used as an effective adjunctive ablation strategy for patients with persistent AF (PsAF), it can result in iatrogenic scar-related atrial tachycardia (iAT) requiring additional ablation. Personalized atrial digital twins (DTs) have been used preprocedurally to devise ablation targeting that eliminate the fibrotic substrate arrhythmogenic propensity and could potentially be used to predict and prevent postablation iAT. OBJECTIVES: In this study, the authors sought to explore possible alternative configurations of ablation lesions that could prevent iAT occurrence with the use of biatrial DTs of prospectively enrolled PsAF patients. METHODS: Biatrial DTs were generated from late gadolinium enhancement-magnetic resonance images of 37 consecutive PsAF patients, and the fibrotic substrate locations in the DT capable of sustaining reentries were determined. These locations were ablated in DTs by representing a single compound region of ablation with normal power (SSA), and postablation iAT occurrence was determined. At locations of iAT, ablation at the same DT target was repeated, but applying multiple lesions of reduced-strength (MRA) instead of SSA. RESULTS: Eighty-three locations in the fibrotic substrates of 28 personalized biatrial DTs were capable of sustaining reentries and were thus targeted for SSA ablation. Of these ablations, 45 resulted in iAT. Repeating the ablation at these targets with MRA instead of SSA resulted in the prevention of iAT occurrence at 15 locations (18% reduction in the rate of iAT occurrence). CONCLUSIONS: Personalized atrial DTs enable preprocedure prediction of iAT occurrence after ablation in the fibrotic substrate. It also suggests MRA could be a potential strategy for preventing postablation AT.

20.
J Int Med Res ; 52(9): 3000605241274550, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39253830

ABSTRACT

OBJECTIVE: In this observational study, we determined the distribution of mHealth applications (apps) in Germany using data from the FeverApp registry. METHODS: The registry data were processed to assess general monthly trends in app distribution, and a seasonal autoregressive integrated moving average model was decomposed to investigate time series. A sample comparison was made matching data from cold-called against self-registered distributers of the FeverApp. RESULTS: Among 881 pediatric and adolescent medical practices, 27,300 app users were recruited between 2019 and August 2023. The number of monthly recruited users increased steadily. A seasonal trend was observed, showing a higher distribution in winter months. Self-registered pediatric practices did not recruit significantly more app users than cold-called practices, with approximately every 25th family recruited in both groups. CONCLUSIONS: The trend of more app sign-ups during winter is likely related to the flu season in Germany. Intrinsic and extrinsic motivational factors of the practices seem to have a large impact on the distribution. We observed a positive trend in the app distribution. Seasonal febrile infections and individual distribution methods among practices influence the distribution of the FeverApp in Germany. Family factors may have a greater influence than the motivation of distributing practices.


Subject(s)
Mobile Applications , Registries , Telemedicine , Humans , Germany/epidemiology , Adolescent , Child , Female , Male , Seasons , Fever/epidemiology , Fever/diagnosis
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